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1.
Artigo em Inglês | MEDLINE | ID: mdl-38839368

RESUMO

Esophagogastric junction cancer (EGJC) is a rare malignant disease that occurs in the gastroesophageal transition zone. In recent years, its incidence has been rapidly increasing not only in Western countries but also in East Asia, and it has been attracting the attention of both clinicians and researchers. EGJC has a worse prognosis than gastric cancer (GC) and is characterized by complex lymphatic drainage pathways in the mediastinal and abdominal regions. EGJC was previously treated in the same way as GC or esophageal cancer, but, in recent years, it has been treated as an independent malignant disease, and treatment focusing only on EGJC has been developed. A recent multicenter prospective study revealed the frequency of lymph node metastasis by station and established the optimal extent of lymph node dissection. In perioperative treatment, the combination of multi-drug chemotherapy, radiation therapy, molecular targeted therapy, and immunotherapy is expected to improve the prognosis. In this review, we summarize previous clinical trials and their important evidence on surgical and perioperative treatments for EGJC.


Assuntos
Neoplasias Esofágicas , Esofagectomia , Junção Esofagogástrica , Humanos , Junção Esofagogástrica/cirurgia , Junção Esofagogástrica/patologia , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/cirurgia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/terapia , Resultado do Tratamento , Esofagectomia/efeitos adversos , Esofagectomia/mortalidade , Gastrectomia/mortalidade , Gastrectomia/efeitos adversos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Neoplasias Gástricas/terapia , Excisão de Linfonodo , Quimioterapia Adjuvante , Metástase Linfática , Fatores de Risco , Terapia Neoadjuvante/efeitos adversos , Terapia Neoadjuvante/mortalidade
2.
BMC Cancer ; 24(1): 691, 2024 Jun 06.
Artigo em Inglês | MEDLINE | ID: mdl-38844880

RESUMO

PURPOSE: The potential efficacy of metformin in breast cancer (BC) has been hotly discussed but never conclusive. This genetics-based study aimed to evaluate the relationships between metformin targets and BC risk. METHODS: Metformin targets from DrugBank and genome-wide association study (GWAS) data from IEU OpenGWAS and FinnGen were used to investigate the breast cancer (BC)-metformin causal link with various Mendelian Randomization (MR) methods (e.g., inverse-variance-weighting). The genetic association between type 2 diabetes (T2D) and the drug target of metformin was also analyzed as a positive control. Sensitivity and pleiotropic tests ensured reliability. RESULTS: The primary targets of metformin are PRKAB1, ETFDH and GPD1L. We found a causal association between PRKAB1 and T2D (odds ratio [OR] 0.959, P = 0.002), but no causal relationship was observed between metformin targets and overall BC risk (PRKAB1: OR 0.990, P = 0.530; ETFDH: OR 0.986, P = 0.592; GPD1L: OR 1.002, P = 0.806). A noteworthy causal relationship was observed between ETFDH and estrogen receptor (ER)-positive BC (OR 0.867, P = 0.018), and between GPD1L and human epidermal growth factor receptor 2 (HER2)-negative BC (OR 0.966, P = 0.040). Other group analyses did not yield positive results. CONCLUSION: The star target of metformin, PRKAB1, does not exhibit a substantial causal association with the risk of BC. Conversely, metformin, acting as an inhibitor of ETFDH and GPD1L, may potentially elevate the likelihood of developing ER-positive BC and HER2-negative BC. Consequently, it is not advisable to employ metformin as a standard supplementary therapy for BC patients without T2D.


Assuntos
Neoplasias da Mama , Diabetes Mellitus Tipo 2 , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Metformina , Humanos , Metformina/uso terapêutico , Metformina/farmacologia , Neoplasias da Mama/genética , Neoplasias da Mama/tratamento farmacológico , Feminino , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/complicações , Quimioterapia Adjuvante/métodos , Hipoglicemiantes/uso terapêutico , Polimorfismo de Nucleotídeo Único
3.
BMC Womens Health ; 24(1): 324, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38834997

RESUMO

BACKGROUND: Whether patients with cT1 - 2N1M0 breast cancer can benefit from postoperative radiotherapy (RT) after receiving neoadjuvant chemotherapy (NAC) has been controversial. Therefore, the purpose of this study was to explore whether postoperative RT can benefit this group of patients in terms of survival. METHODS: We used Surveillance, Epidemiology, and End Results (SEER) data to conduct a retrospective review of women with cT1 - 2N1M0 breast cancer diagnosed between 20 and 80 years of age who received NAC between 2010 and 2015. Our study compared the impact of postoperative RT on overall survival (OS) and cancer-specific survival (CSS) in breast cancer patients using propensity score matching (PSM) and performed subgroup analysis. RESULTS: This study finally included 1092 cT1 - 2N1M0 breast cancer patients. Regardless of the patient's PSM status, postoperative RT was significantly associated with OS of cT1-2N1M0 breast cancer patients who received NAC. Specifically, the 10-year OS rate was 78.7% before PSM matching, compared with 71.1% in patients who did not receive postoperative RT, and the difference was more significant after PSM matching, which was 83.1% and 71.1% respectively. However, postoperative RT did not significantly benefit CSS in patients with cT1 - 2N1M0 breast cancer who received NAC. The 10-year CSS rate was 81.4% VS 76.2% (P = 0.085) before PSM matching and 85.8% VS 76.2%(P = 0.076) after matching. Due to the intersection of OS and CSS curves, this restricted mean survival time (RMST) method was chosen as a supplement. After 60 months, the OS difference in RMST between the postoperative RT group and the non-radiotherapy (noRT) group was 7.37 months (95%CI: 0.54-14.21; P = 0.034), and the CSS difference was 5.18 months (95%CI: -1.31-11.68; P = 0.118). Subgroup analysis found that in patients with right-sided breast cancer, postoperative RT improved the patient's OS (HR = 0.45, 95%CI: 0.21-0.95, P = 0.037) and CSS (HR = 0.42, 95%CI: 0.18-0.98, P = 0.045). CONCLUSIONS: Our results showed that additional postoperative RT improved the OS of cT1 - 2N1M0 breast cancer patients who received NAC, but failed to improve their CSS. It is worth noting that in the subgroup analysis of patients with right-sided breast cancer, we observed significant improvements in OS and CSS. And further prospective studies are still needed to verify the effect of postoperative RT in different subgroups.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Programa de SEER , Humanos , Feminino , Neoplasias da Mama/terapia , Neoplasias da Mama/mortalidade , Neoplasias da Mama/radioterapia , Neoplasias da Mama/tratamento farmacológico , Terapia Neoadjuvante/métodos , Terapia Neoadjuvante/estatística & dados numéricos , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto , Idoso , Radioterapia Adjuvante , Estadiamento de Neoplasias , Quimioterapia Adjuvante/métodos , Período Pós-Operatório , Idoso de 80 Anos ou mais , Pontuação de Propensão , Taxa de Sobrevida , Adulto Jovem
4.
Support Care Cancer ; 32(7): 410, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38839667

RESUMO

PURPOSE: Alopecia is a common side-effect of chemotherapy and can be extremely distressing to patients. Scalp cooling can be used to reduce hair loss, but the optimal duration of cooling remains unclear. Our aim was to determine whether increasing the duration of scalp cooling improves hair preservation. METHODS: Patients with HER2-negative, non-metastatic, breast cancer received scalp cooling during adjuvant chemotherapy: three cycles of epirubicin/cyclophosphamide (EC) followed by three cycles of paclitaxel. The patients were randomly assigned to two groups. Group A (n=18) wore a Paxman cooling cap during each infusion and for 30 min post-infusion while Group B (n=19) wore the cap from 30 min before to 2 h after each infusion. All patients were asked to complete a questionnaire recording hair loss/regrowth, adverse events, and quality of life. Success of treatment was defined as <50% hair loss. RESULTS: The success rates after each of the three cycles did not differ significantly between the two groups (EC: Group A: 40%, Group B: 44%; paclitaxel: Group A: 50%, Group B: 36%; p>0.05). Hair regrowth was significantly higher in Group B at the 8-week follow-up, but not at the 6-month follow-up. Head discomfort affected more patients in Group B than in Group A during the first session (94% vs. 62%, respectively; p=0.039). CONCLUSION: Long duration scalp cooling during chemotherapy might increase patients' discomfort and does not appear to improve hair preservation.


Assuntos
Alopecia , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias da Mama , Ciclofosfamida , Epirubicina , Paclitaxel , Qualidade de Vida , Couro Cabeludo , Humanos , Alopecia/prevenção & controle , Alopecia/induzido quimicamente , Feminino , Neoplasias da Mama/tratamento farmacológico , Projetos Piloto , Pessoa de Meia-Idade , Quimioterapia Adjuvante/métodos , Quimioterapia Adjuvante/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Ciclofosfamida/administração & dosagem , Ciclofosfamida/efeitos adversos , Paclitaxel/administração & dosagem , Paclitaxel/efeitos adversos , Adulto , Epirubicina/administração & dosagem , Epirubicina/efeitos adversos , Hipotermia Induzida/métodos , Fatores de Tempo , Idoso , Inquéritos e Questionários
5.
PeerJ ; 12: e17492, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38827304

RESUMO

Background: The promising efficacy of novel anti-HER2 antibody-drug conjugates (ADC) in HER2-low breast cancer has made HER2-low a research hotspot. However, controversy remains regarding the neoadjuvant chemotherapy (NAC) efficacy, prognosis, and the relationship with hormone receptor (HR) status of HER2-low. Methods: A retrospective analysis was conducted on 975 patients with HER2-negative breast cancer undergoing NAC at Tianjin Medical University Cancer Institute and Hospital, evaluating pathological complete response (pCR) rate and prognosis between HER2-low and HER2-zero in the overall cohort and subgroups. Results: Overall, 579 (59.4%) and 396 (40.6%) patients were HER2-low and HER2-zero disease, respectively. Compared with HER2-zero, the HER2-low cohort consists of more postmenopausal patients, with lower histological grade and higher HR positivity. In the HR-positive subgroup, HER2-low cases remain to exhibit lower histological grade, while in the HR-negative subgroup, they show higher grade. The HER2-low group had lower pCR rates than the HER2-zero group (16.4% vs. 24.0%). In the HR-positive subgroup, HER2-low consistently showed lower pCR rate (8.1% vs. 15.5%), and served as an independent suppressive factor for the pCR rate. However, no significant difference was observed in the pCR rates between HER2-low and HER2-zero in the HR-negative breast cancer. In the entire cohort and in stratified subgroups based on HR and pCR statuses, no difference in disease-free survival were observed between HER2-low and HER2-zero. Conclusions: In the Chinese population, HER2-low breast cancer exhibits distinct characteristics and efficacy of NAC in different HR subgroups. Its reduced pCR rate in HR-positive subgroup is particularly important for clinical decisions. However, HER2-low is not a reliable factor for assessing long-term survival outcomes.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Receptor ErbB-2 , Humanos , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/mortalidade , Feminino , Estudos Retrospectivos , Receptor ErbB-2/metabolismo , Receptor ErbB-2/genética , Pessoa de Meia-Idade , Terapia Neoadjuvante/métodos , China/epidemiologia , Prognóstico , Adulto , Idoso , Quimioterapia Adjuvante , Resultado do Tratamento , Receptores de Estrogênio/metabolismo , Receptores de Progesterona/metabolismo
6.
Cancer Med ; 13(11): e7326, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38826114

RESUMO

BACKGROUND: Optimal adjuvant chemotherapy after laparoscopic surgery in gastric cancer (GC) patients is still undefined. We aimed to evaluate the efficacy of S-1 plus oxaliplatin (SOX) and capecitabine plus oxaliplatin (CAPOX) in patients with GC after laparoscopic gastrectomy. METHODS: A non-inferiority randomized controlled clinical trial was performed in China. Patients with advanced GC who underwent laparoscopic D2 gastrectomy were randomly assigned to receive SOX and CAPOX regimens. RESULTS: In total, 191 patients were screened between May 2018 and June 2019, and 140 (73.3%) were included in the modified intent-to-treat analysis (mITT), of whom 69 and 71 were assigned to the SOX and CAPOX groups, respectively. The SOX group had similar 3-year overall survival (OS) and disease-free survival to the CAPOX group. Subgroup analysis revealed significantly better OS in the SOX group for male patients ([HR] = 0.395; 95% [CI], 0.153-1.019; p = 0.045), age >60 (HR = 0.219; 95% [CI], 0.064-0.753; p = 0.016), tumors in the gastric antrum (HR = 0.273; 95% [CI], 0.076-0.981; p = 0.047), and moderately differentiated tumors (HR = 0.338; 95% [CI], 0.110-1.041; p = 0.041). There were no significant differences observed in terms of adverse events and recurrence patterns between the two groups. CONCLUSION: Adjuvant SOX was non-inferior to CAPOX treatments for patients with GC who underwent curative laparoscopic D2 gastrectomy. For male patients, aged >60 years, tumors in the gastric antrum, and moderately differentiated tumors, adjuvant SOX may achieve an improvement compared with CAPOX.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Capecitabina , Combinação de Medicamentos , Gastrectomia , Laparoscopia , Oxaliplatina , Ácido Oxônico , Neoplasias Gástricas , Tegafur , Humanos , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/patologia , Neoplasias Gástricas/mortalidade , Masculino , Gastrectomia/métodos , Feminino , Pessoa de Meia-Idade , Laparoscopia/métodos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Oxaliplatina/uso terapêutico , Oxaliplatina/administração & dosagem , Tegafur/uso terapêutico , Tegafur/administração & dosagem , Ácido Oxônico/uso terapêutico , Ácido Oxônico/administração & dosagem , Quimioterapia Adjuvante/métodos , Capecitabina/administração & dosagem , Capecitabina/uso terapêutico , Idoso , Adulto
7.
Hepatol Commun ; 8(6)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38829199

RESUMO

Surgical therapies in patients with early-stage HCC can afford long-term survival but are often limited by the continued risk of recurrence, underscoring an interest in (neo)adjuvant strategies. Prior attempts at adjuvant therapy using tyrosine kinase inhibitors failed to yield significant improvements in recurrence-free survival or overall survival. Advances in the efficacy of systemic therapy options, including the introduction of immune checkpoint inhibitors, have fueled renewed interest in this area. Indeed, the IMBrave050 trial recently demonstrated significant improvements in recurrence-free survival with 1 year of adjuvant atezolizumab plus bevacizumab in high-risk patients undergoing surgical resection or ablation, with several other ongoing trials in this space. There is a strong rationale for consideration of the administration of these therapies in the neoadjuvant setting, supported by early clinical data demonstrating high rates of objective responses, although larger trials examining downstream outcomes are necessary, particularly considering the possible risks of this strategy. In parallel, there has been increased interest in using systemic therapies as a bridging or downstaging strategy for liver transplantation. Current data suggest the short-term safety of this approach, with acceptable rates of rejection, so immunotherapy is not considered a contraindication to transplant; however, larger studies are needed to evaluate the incremental value of this approach over locoregional therapy. Conversely, the use of immunotherapy is currently discouraged after liver transplantation, given the high risk of graft rejection and death. The increasing complexity of HCC management and increased consideration of (neo)adjuvant strategies highlight the critical role of multidisciplinary care when making these decisions.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Terapia Neoadjuvante , Humanos , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/tratamento farmacológico , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/tratamento farmacológico , Quimioterapia Adjuvante , Transplante de Fígado , Inibidores de Checkpoint Imunológico/uso terapêutico , Anticorpos Monoclonais Humanizados/uso terapêutico , Bevacizumab/uso terapêutico , Bevacizumab/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico
8.
Support Care Cancer ; 32(7): 415, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38847977

RESUMO

PURPOSE: Anemia is relatively common in cancer patients, and is associated with poor survival in patients with various malignancies. However, how anemia would affect prognosis and response to neoadjuvant chemotherapy (NAC) in osteosarcoma (OS) is still without substantial evidence. METHODS: We retrospectively analysed 242 patients with stage II OS around the knee joint in our institute. Changed hemoglobin (Hb) levels (before and after NAC) were recorded to assess the prognostic value in DFS (disease-free survival) and tumor response to NAC. Univariate and multivariate analyses were conducted to identify prognostic factors related with outcome in OS patients. RESULTS: The mean Hb level significantly decreased after NAC (134.5 ± 15.3 g/L vs. 117.4 ± 16.3 g/L). The percentage of mild (21%), moderate (4.2%) and severe (0%) anemia patients markedly increased after NAC: 41%, 24% and 4.1% respectively. There was higher percentage of ≥ 5% Hb decline in patients with tumor necrosis rate < 90% (141 out of 161), compared with those with tumor necrosis rate ≥ 90% (59 out of 81). Further univariate and survival analysis demonstrated that Hb decline had a significant role in prediction survival in OS patients. Patients with ≥ 5% Hb decline after NAC had an inferior DFS compared with those with < 5% Hb decline. CONCLUSION: In osteosarcoma, patients with greater Hb decrease during neoadjuvant treatment were shown to have worse DFS and a poorer response to NAC than those without. Attempts to correct anemia and their effects on outcomes for osteosarcoma patients should be explored in future studies.


Assuntos
Anemia , Neoplasias Ósseas , Hemoglobinas , Articulação do Joelho , Terapia Neoadjuvante , Osteossarcoma , Humanos , Osteossarcoma/tratamento farmacológico , Osteossarcoma/mortalidade , Estudos Retrospectivos , Masculino , Feminino , Terapia Neoadjuvante/métodos , Hemoglobinas/análise , Adulto , Prognóstico , Anemia/etiologia , Adolescente , Neoplasias Ósseas/tratamento farmacológico , Neoplasias Ósseas/mortalidade , Adulto Jovem , Criança , Articulação do Joelho/patologia , Intervalo Livre de Doença , Pessoa de Meia-Idade , Análise Multivariada , Quimioterapia Adjuvante/métodos , Índice de Gravidade de Doença
9.
JAMA Netw Open ; 7(5): e249548, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38717774

RESUMO

IMPORTANCE: Diabetes is associated with poorer prognosis of patients with breast cancer. The association between diabetes and adjuvant therapies for breast cancer remains uncertain. OBJECTIVE: To comprehensively examine the associations of preexisting diabetes with radiotherapy, chemotherapy, and endocrine therapy in low-income women with breast cancer. DESIGN, SETTING, AND PARTICIPANTS: This population-based cohort study included women younger than 65 years diagnosed with nonmetastatic breast cancer from 2007 through 2015, followed up through 2016, continuously enrolled in Medicaid, and identified from the linked Missouri Cancer Registry and Medicaid claims data set. Data were analyzed from January 2022 to October 2023. EXPOSURE: Preexisting diabetes. MAIN OUTCOMES AND MEASURES: Logistic regression was used to estimate odds ratios (ORs) of utilization (yes/no), timely initiation (≤90 days postsurgery), and completion of radiotherapy and chemotherapy, as well as adherence (medication possession ratio ≥80%) and persistence (<90-consecutive day gap) of endocrine therapy in the first year of treatment for women with diabetes compared with women without diabetes. Analyses were adjusted for sociodemographic and tumor factors. RESULTS: Among 3704 women undergoing definitive surgery, the mean (SD) age was 51.4 (8.6) years, 1038 (28.1%) were non-Hispanic Black, 2598 (70.1%) were non-Hispanic White, 765 (20.7%) had a diabetes history, 2369 (64.0%) received radiotherapy, 2237 (60.4%) had chemotherapy, and 2505 (67.6%) took endocrine therapy. Compared with women without diabetes, women with diabetes were less likely to utilize radiotherapy (OR, 0.67; 95% CI, 0.53-0.86), receive chemotherapy (OR, 0.67; 95% CI, 0.48-0.93), complete chemotherapy (OR, 0.71; 95% CI, 0.50-0.99), and be adherent to endocrine therapy (OR, 0.71; 95% CI, 0.56-0.91). There were no significant associations of diabetes with utilization (OR, 0.95; 95% CI, 0.71-1.28) and persistence (OR, 1.09; 95% CI, 0.88-1.36) of endocrine therapy, timely initiation of radiotherapy (OR, 1.09; 95% CI, 0.86-1.38) and chemotherapy (OR, 1.09; 95% CI, 0.77-1.55), or completion of radiotherapy (OR, 1.25; 95% CI, 0.91-1.71). CONCLUSIONS AND RELEVANCE: In this cohort study, preexisting diabetes was associated with subpar adjuvant therapies for breast cancer among low-income women. Improving diabetes management during cancer treatment is particularly important for low-income women with breast cancer who may have been disproportionately affected by diabetes and are likely to experience disparities in cancer treatment and outcomes.


Assuntos
Neoplasias da Mama , Diabetes Mellitus , Pobreza , Humanos , Feminino , Neoplasias da Mama/terapia , Neoplasias da Mama/epidemiologia , Pessoa de Meia-Idade , Pobreza/estatística & dados numéricos , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia , Adulto , Estados Unidos/epidemiologia , Medicaid/estatística & dados numéricos , Estudos de Coortes , Missouri/epidemiologia , Quimioterapia Adjuvante/estatística & dados numéricos , Adesão à Medicação/estatística & dados numéricos
10.
BMC Surg ; 24(1): 140, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720305

RESUMO

BACKGROUND: We investigated the real-world efficacy of adjuvant therapy for stage I lung adenocarcinoma patients with pathological high-risk factors. METHODS: Study participants were enrolled from November 1, 2016 and December 31, 2020. Clinical bias was balanced by propensity score matching. Disease-free survival (DFS) outcomes were compared by Kaplan-Meier analysis. The Cox proportional hazards regression was used to identify survival-associated factors. p ≤ 0.05 was the threshold for statistical significance. RESULTS: A total of 454 patients, among whom 134 (29.5%) underwent adjuvant therapy, were enrolled in this study. One hundred and eighteen of the patients who underwent adjuvant therapy were well matched with non-treatment patients. Prognostic outcomes of the treatment group were significantly better than those of the non-treatment group, as revealed by Kaplan-Meier analysis after PSM. Differences in prevention of recurrence or metastasis between the targeted therapy and chemotherapy groups were insignificant. Adjuvant therapy was found to be positive prognostic factors, tumor size and solid growth patterns were negative. CONCLUSIONS: Adjuvant therapy significantly improved the DFS for stage I lung adenocarcinoma patients with high-risk factors. Larger prospective clinical trials should be performed to verify our findings.


Assuntos
Adenocarcinoma de Pulmão , Neoplasias Pulmonares , Estadiamento de Neoplasias , Pontuação de Propensão , Humanos , Feminino , Masculino , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/cirurgia , Neoplasias Pulmonares/terapia , Neoplasias Pulmonares/mortalidade , Pessoa de Meia-Idade , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/cirurgia , Adenocarcinoma de Pulmão/terapia , Adenocarcinoma de Pulmão/mortalidade , Quimioterapia Adjuvante , Fatores de Risco , Idoso , Estudos Retrospectivos , Resultado do Tratamento , Pneumonectomia/métodos , Intervalo Livre de Doença , Prognóstico , Estimativa de Kaplan-Meier
11.
Investig Clin Urol ; 65(3): 256-262, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38714516

RESUMO

PURPOSE: We evaluated the risk factors associated with failure to complete gemcitabine-cisplatin (GP) neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC). MATERIALS AND METHODS: In total, 231 patients with MIBC treated with NAC before undergoing radical cystectomy between 2013 and 2022 participated in this study. Logistic regression analysis was performed to assess the relationship between the likelihood of incomplete NAC and clinical and demographic variables, including age, sex, hypertension (HTN), diabetes mellitus (DM), prechemotherapy glomerular filtration rate, clinical T stage, clinical N stage, and body mass index (BMI). RESULTS: Of 231 patients, 209 (90.5%) and 22 (9.5%) completed and discontinued the NAC course, respectively. The mean age was 66.13±9.15, 65.63±9.07, and 70.86±8.66 years for the total sample, continuation, and discontinuation groups, respectively (p=0.010). No significant inter-group differences in sex, HTN, height, weight, BMI, pre-chemotherapy glomerular filtration rate, clinical T stage, or clinical N stage were observed. According to the results of the multivariable analysis, age (odds ratio [OR] 1.076, 95% confidence interval [CI] 1.013-1.143, p=0.018) and the presence of DM (OR 2.541, 95% CI 1.028-6.281, p=0.043) were significantly associated with NAC discontinuation. CONCLUSIONS: Thus, older age and presence of DM are potential risk factors for GP NAC discontinuation in patients with MIBC. Further studies are required to validate our findings and develop strategies to minimize the rate of GP NAC discontinuation in this population.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica , Cisplatino , Desoxicitidina , Gencitabina , Terapia Neoadjuvante , Invasividade Neoplásica , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Neoplasias da Bexiga Urinária/cirurgia , Masculino , Cisplatino/administração & dosagem , Feminino , Idoso , Desoxicitidina/análogos & derivados , Desoxicitidina/administração & dosagem , Fatores de Risco , Pessoa de Meia-Idade , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Estudos Retrospectivos , Falha de Tratamento , Cistectomia/métodos , Quimioterapia Adjuvante
12.
Int Ophthalmol ; 44(1): 210, 2024 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-38691217

RESUMO

PURPOSE: To evaluate the effect of adjuvant Mitomycin C (MMC) use on the anatomical and functional success of vitreoretinal surgery (VRS) in severe diabetic tractional retinal detachment (dTRD) patients. METHODS: A retrospective analysis of consecutive patients undergoing VRS due to severe dTRD was conducted. Patients were categorized into those who received 20 µg/0.1 mL MMC via MMC sandwich method (Group 1) and those who did not (Group 2). Demographics, surgical characteristics, visual outcomes, and complications that may related to MMC were analyzed. RESULTS: A total of 25 eyes were included, 13 in Group 1 and 12 in Group 2. No statistical difference was observed in baseline characteristics between the groups. The mean best-corrected visual acuity was 1.90 ± 0.43 logMAR and 1.93 ± 0.41 logMAR preoperatively and 1.60 ± 0.78 logMAR and 1.56 ± 0.78 logMAR postoperatively in Groups 1 and 2, respectively (p = 0.154). The postoperative mean intraocular pressure was 16.23 ± 2.55 mmHg and 13.08 ± 4.94 mmHg in Groups 1 and 2, respectively (p = 0.225). The rate of re-surgery was significantly lower in Group 1 (0% vs. 41.7% in Group 2, p = 0.015). Retina was attached in all patients at the last visit. No MMC-related complication was recorded. CONCLUSION: Intraoperative adjuvant MMC application for severe dTRD significantly reduces re-surgery rates with good anatomical and functional outcomes safely.


Assuntos
Retinopatia Diabética , Mitomicina , Descolamento Retiniano , Acuidade Visual , Vitrectomia , Humanos , Estudos Retrospectivos , Masculino , Feminino , Mitomicina/administração & dosagem , Vitrectomia/métodos , Pessoa de Meia-Idade , Retinopatia Diabética/complicações , Retinopatia Diabética/fisiopatologia , Retinopatia Diabética/diagnóstico , Retinopatia Diabética/cirurgia , Descolamento Retiniano/cirurgia , Descolamento Retiniano/diagnóstico , Idoso , Resultado do Tratamento , Quimioterapia Adjuvante/métodos , Alquilantes/administração & dosagem , Seguimentos , Adulto
13.
Oncoimmunology ; 13(1): 2347441, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38694625

RESUMO

In clinical practice, the administration of adjuvant chemotherapy (ACT) following tumor surgical resection raises a critical dilemma for stage II colon cancer (CC) patients. The prognostic features used to identify high-risk CC patients rely on the pathological assessment of tumor cells. Currently, these factors are considered for stratifying patients who may benefit from ACT at early CC stages. However, the extent to which these factors predict clinical outcomes (i.e. recurrence, survival) remains highly controversial, also uncertainty persists regarding patients' response to treatment, necessitating further investigation. Therefore, an imperious need is to explore novel biomarkers that can reliably stratify patients at risk, to optimize adjuvant treatment decisions. Recently, we evaluated the prognostic and predictive value of Immunoscore (IS), an immune digital-pathology assay, in stage II CC patients. IS emerged as the sole significant parameter for predicting disease-free survival (DFS) in high-risk patients. Moreover, IS effectively stratified patients who would benefit most from ACT based on their risk of recurrence, thus predicting their outcomes. Notably, our findings revealed that digital IS outperformed the visual quantitative assessment of the immune response conducted by expert pathologists. The latest edition of the WHO classification for digestive tumor has introduced the evaluation of the immune response, as assessed by IS, as desirable and essential diagnostic criterion. This supports the revision of current cancer guidelines and strongly recommends the implementation of IS into clinical practice as a patient stratification tool, to guide CC treatment decisions. This approach may provide appropriate personalized therapeutic decisions that could critically impact early-stage CC patient care.


Assuntos
Neoplasias do Colo , Humanos , Neoplasias do Colo/imunologia , Neoplasias do Colo/patologia , Medição de Risco , Quimioterapia Adjuvante , Prognóstico , Estadiamento de Neoplasias , Biomarcadores Tumorais/metabolismo , Recidiva Local de Neoplasia/imunologia , Intervalo Livre de Doença
14.
Cancer Med ; 13(9): e7229, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38698688

RESUMO

AIM: To investigate the relationship between chemoresistance in pancreatic cancer patients receiving postoperative gemcitabine adjuvant therapy and specific clinical/pathological characteristics, as well as its impact on patient prognosis. METHODS: From June 2018 to June 2021, clinical and pathological data of 148 pancreatic cancer patients were collected, and 101 patients were followed up for tumor recurrence/metastasis and survival status. The correlation between chemoresistance and specific clinical/pathological characteristics or patient prognosis was retrospectively analyzed. RESULTS: Of the 148 patients, 78 were in the chemoresistance group and 70 in the non-chemoresistance group. Univariate analysis showed that the development of chemoresistance may be related to patient age, combined diabetes, preoperative CA19-9 level, tumor size, AJCC stage, vascular invasion, and positive lymph node ratio. Furthermore, subsequent multivariate analysis incorporating these variables indicated that tumor size may be a key factor influencing chemoresistance (p < 0.001, OR = 1.584). Log-rank test showed patients in the chemoresistance group had worse overall survival (OS) (HR = 2.102, p = 0.018) and progression free survival (PFS) (HR = 3.208, p = 0.002) than patients in the non-chemoresistance group; and patients with smaller size tumors (diameter ≤3 cm) had significantly better OS (HR = 2.923, p < 0.001) and PFS (HR = 2.930, p = 0.003) than those with larger size tumors (diameter >3 cm). CONCLUSIONS: Patients with pancreatic cancer receiving postoperative gemcitabine adjuvant therapy are more likely to develop chemoresistance when their tumor sizes are larger (diameter >3 cm). Development of chemoresistance exacerbates the prognosis of patients with pancreatic cancer, and larger tumor size is also a risk factor for poor prognosis in these patients.


Assuntos
Antimetabólitos Antineoplásicos , Desoxicitidina , Resistencia a Medicamentos Antineoplásicos , Gencitabina , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Neoplasias Pancreáticas/mortalidade , Neoplasias Pancreáticas/cirurgia , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico , Masculino , Feminino , Quimioterapia Adjuvante/métodos , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos , Idoso , Antimetabólitos Antineoplásicos/uso terapêutico , Adulto , Recidiva Local de Neoplasia
15.
J Cancer Res Clin Oncol ; 150(5): 223, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38691204

RESUMO

OBJECTIVE: To investigate the clinical value of contrast-enhanced computed tomography (CECT) radiomics for predicting the response of primary lesions to neoadjuvant chemotherapy in hepatoblastoma. METHODS: Clinical and CECT imaging data were retrospectively collected from 116 children with hepatoblastoma who received neoadjuvant chemotherapy. Tumor response was assessed according to the Response Evaluation Criteria in Solid Tumors (RECIST). Subsequently, they were randomly stratified into a training cohort and a test cohort in a 7:3 ratio. The clinical model was constructed using univariate and multivariate logistic regression, while the radiomics model was developed based on selected radiomics features employing the support vector machine algorithm. The combined clinical-radiomics model incorporated both clinical and radiomics features. RESULTS: The area under the curve (AUC) for the clinical, radiomics, and combined models was 0.704 (95% CI: 0.563-0.845), 0.830 (95% CI: 0.704-0.959), and 0.874 (95% CI: 0.768-0.981) in the training cohort, respectively. In the validation cohort, the combined model achieved the highest mean AUC of 0.830 (95% CI 0.616-0.999), with a sensitivity, specificity, accuracy, precision, and f1 score of 72.0%, 81.1%, 78.5%, 57.2%, and 63.5%, respectively. CONCLUSION: CECT radiomics has the potential to predict primary lesion response to neoadjuvant chemotherapy in hepatoblastoma.


Assuntos
Meios de Contraste , Hepatoblastoma , Neoplasias Hepáticas , Terapia Neoadjuvante , Tomografia Computadorizada por Raios X , Humanos , Hepatoblastoma/tratamento farmacológico , Hepatoblastoma/diagnóstico por imagem , Hepatoblastoma/patologia , Terapia Neoadjuvante/métodos , Feminino , Masculino , Neoplasias Hepáticas/diagnóstico por imagem , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/patologia , Tomografia Computadorizada por Raios X/métodos , Estudos Retrospectivos , Pré-Escolar , Lactente , Criança , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Quimioterapia Adjuvante/métodos , Radiômica
16.
J Med Case Rep ; 18(1): 233, 2024 May 02.
Artigo em Inglês | MEDLINE | ID: mdl-38693541

RESUMO

INTRODUCTION: Vaginal metastasis from colorectal cancer is a rare occurrence, typically associated with other metastatic lesions. Isolated metastasis is exceedingly uncommon, with only a few cases documented in the literature. Vaginal involvement in colorectal cancer primarily results from direct contiguous spread from the primary tumor. CASE PRESENTATION: We present the case of a 70-year-old African woman diagnosed with adenocarcinoma of the middle rectum. She underwent chemotherapy, radiotherapy, and subsequent anterior resection. After 2 months, an isolated metastasis of rectal cancer was identified in the lower third of the left vaginal wall, confirmed by biopsy. Colonoscopy ruled out colorectal recurrence. Thoraco-abdominal computed tomography scan showed no distant metastases. The patient underwent abdominoperineal resection, removing the lateral and posterior vaginal wall with free macroscopic margins and a definitive colostomy. The final histopathological analysis confirmed the diagnosis of moderately differentiated adenocarcinoma of the vagina, measuring 5 × 4.5 cm. The rectal wall was extrinsically invaded by the tumor down to the muscularis propria while respecting the rectal mucosa. Resection margins were negative. The patient was discharged 1 week postoperation with no complications. Adjuvant chemotherapy was indicated, and the patient is currently tolerating the treatment well. CONCLUSION: Vaginal metastases from colorectal cancer are extremely rare. A vigilant gynecological examination is recommended during the follow-up of colorectal cancer patients. Diagnosis can be challenging, especially if the metastatic lesion is small and asymptomatic, even after standard radiological examination. Surgical resection followed by chemotherapy is a valid option for patients with early isolated metastases.


Assuntos
Adenocarcinoma , Neoplasias Retais , Neoplasias Vaginais , Idoso , Feminino , Humanos , Adenocarcinoma/diagnóstico por imagem , Adenocarcinoma/patologia , Quimioterapia Adjuvante , Neoplasias Retais/patologia , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Vagina/patologia , Neoplasias Vaginais/secundário , Neoplasias Vaginais/terapia
17.
World J Surg Oncol ; 22(1): 123, 2024 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-38711136

RESUMO

BACKGROUND: Adjuvant chemotherapy (AC) improves the prognosis after pancreatic ductal adenocarcinoma (PDAC) resection. However, previous studies have shown that a large proportion of patients do not receive or complete AC. This national study examined the risk factors for the omission or interruption of AC. METHODS: Data of all patients who underwent pancreatic surgery for PDAC in France between January 2012 and December 2017 were extracted from the French National Administrative Database. We considered "omission of adjuvant chemotherapy" (OAC) all patients who failed to receive any course of gemcitabine within 12 postoperative weeks and "interruption of AC" (IAC) was defined as less than 18 courses of AC. RESULTS: A total of 11 599 patients were included in this study. Pancreaticoduodenectomy was the most common procedure (76.3%), and 31% of the patients experienced major postoperative complications. OACs and IACs affected 42% and 68% of the patients, respectively. Ultimately, only 18.6% of the cohort completed AC. Patients who underwent surgery in a high-volume centers were less affected by postoperative complications, with no impact on the likelihood of receiving AC. Multivariate analysis showed that age ≥ 80 years, Charlson comorbidity index (CCI) ≥ 4, and major complications were associated with OAC (OR = 2.19; CI95%[1.79-2.68]; OR = 1.75; CI95%[1.41-2.18] and OR = 2.37; CI95%[2.15-2.62] respectively). Moreover, age ≥ 80 years and CCI 2-3 or ≥ 4 were also independent risk factors for IAC (OR = 1.54, CI95%[1.1-2.15]; OR = 1.43, CI95%[1.21-1.68]; OR = 1.47, CI95%[1.02-2.12], respectively). CONCLUSION: Sequence surgery followed by chemotherapy is associated with a high dropout rate, especially in octogenarian and comorbid patients.


Assuntos
Carcinoma Ductal Pancreático , Pancreatectomia , Neoplasias Pancreáticas , Humanos , Feminino , Masculino , Neoplasias Pancreáticas/cirurgia , Neoplasias Pancreáticas/tratamento farmacológico , Neoplasias Pancreáticas/patologia , Idoso , Quimioterapia Adjuvante/estatística & dados numéricos , Quimioterapia Adjuvante/métodos , França/epidemiologia , Carcinoma Ductal Pancreático/cirurgia , Carcinoma Ductal Pancreático/tratamento farmacológico , Carcinoma Ductal Pancreático/patologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Prognóstico , Pancreatectomia/estatística & dados numéricos , Seguimentos , Pancreaticoduodenectomia/estatística & dados numéricos , Pancreaticoduodenectomia/métodos , Complicações Pós-Operatórias/epidemiologia , Taxa de Sobrevida , Estudos Retrospectivos , Gencitabina , Fatores de Risco , Desoxicitidina/análogos & derivados , Desoxicitidina/uso terapêutico
18.
Br J Surg ; 111(5)2024 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-38801441

RESUMO

BACKGROUND: Systemic inflammatory response markers have been found to have a prognostic role in several cancers, but their value in predicting the response to neoadjuvant chemotherapy in breast cancer is uncertain. A systematic review and meta-analysis of the literature was carried out to investigate this. METHODS: A systematic search of electronic databases was conducted to identify studies that explored the predictive value of circulating systemic inflammatory response markers in patients with breast cancer before commencing neoadjuvant therapy. A meta-analysis was undertaken for each inflammatory marker where three or more studies reported pCR rates in relation to the inflammatory marker. Outcome data are reported as ORs and 95% confidence intervals. RESULTS: A total of 49 studies were included, of which 42 were suitable for meta-analysis. A lower pretreatment neutrophil-to-lymphocyte ratio was associated with an increased pCR rate (pooled OR 1.66 (95% c.i. 1.32 to 2.09); P < 0.001). A lower white cell count (OR 1.96 (95% c.i. 1.29 to 2.97); P = 0.002) and a lower monocyte count (OR 3.20 (95% c.i. 1.71 to 5.97); P < 0.001) were also associated with a pCR. A higher lymphocyte count was associated with an increased pCR rate (OR 0.44 (95% c.i. 0.30 to 0.64); P < 0.001). CONCLUSION: The present study found the pretreatment neutrophil-to-lymphocyte ratio, white cell count, lymphocyte count, and monocyte count of value in the prediction of a pCR in the neoadjuvant treatment of breast cancer. Further research is required to determine their value in specific breast cancer subtypes and to establish optimal cut-off values, before their adoption in clinical practice.


Assuntos
Neoplasias da Mama , Terapia Neoadjuvante , Feminino , Humanos , Biomarcadores Tumorais/sangue , Neoplasias da Mama/sangue , Neoplasias da Mama/terapia , Neoplasias da Mama/tratamento farmacológico , Quimioterapia Adjuvante , Contagem de Leucócitos , Contagem de Linfócitos , Neutrófilos , Valor Preditivo dos Testes , Prognóstico
19.
BMC Cancer ; 24(1): 578, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734620

RESUMO

OBJECTIVE: This study aims to develop a nomogram integrating inflammation (NLR), Prognostic Nutritional Index (PNI), and EBV DNA (tumor burden) to achieve personalized treatment and prediction for stage IVA NPC. Furthermore, it endeavors to pinpoint specific subgroups that may derive significant benefits from S-1 adjuvant chemotherapy. METHODS: A total of 834 patients diagnosed with stage IVA NPC were enrolled in this study and randomly allocated into training and validation cohorts. Multivariate Cox analyses were conducted to identify independent prognostic factors for constructing the nomogram. The predictive and clinical utility of the nomogram was assessed through measures including the AUC, calibration curve, DCA, and C-indexes. IPTW was employed to balance baseline characteristics across the population. Kaplan-Meier analysis and log-rank tests were utilized to evaluate the prognostic value. RESULTS: In our study, we examined the clinical features of 557 individuals from the training cohort and 277 from the validation cohort. The median follow-up period was 50.1 and 49.7 months, respectively. For the overall cohort, the median follow-up duration was 53.8 months. The training and validation sets showed 3-year OS rates of 87.7% and 82.5%, respectively. Meanwhile, the 3-year DMFS rates were 95.9% and 84.3%, respectively. We created a nomogram that combined PNI, NRI, and EBV DNA, resulting in high prediction accuracy. Risk stratification demonstrated substantial variations in DMFS and OS between the high and low risk groups. Patients in the high-risk group benefited significantly from the IC + CCRT + S-1 treatment. In contrast, IC + CCRT demonstrated non-inferior 3-year DMFS and OS compared to IC + CCRT + S-1 in the low-risk population, indicating the possibility of reducing treatment intensity. CONCLUSIONS: In conclusion, our nomogram integrating NLR, PNI, and EBV DNA offers precise prognostication for stage IVA NPC. S-1 adjuvant chemotherapy provides notable benefits for high-risk patients, while treatment intensity reduction may be feasible for low-risk individuals.


Assuntos
Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Estadiamento de Neoplasias , Nomogramas , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo/tratamento farmacológico , Carcinoma Nasofaríngeo/mortalidade , Carcinoma Nasofaríngeo/patologia , Quimioterapia Adjuvante/métodos , Prognóstico , Neoplasias Nasofaríngeas/tratamento farmacológico , Neoplasias Nasofaríngeas/mortalidade , Neoplasias Nasofaríngeas/patologia , Inflamação , Adulto , Avaliação Nutricional , Herpesvirus Humano 4/isolamento & purificação , Tegafur/uso terapêutico , Tegafur/administração & dosagem , DNA Viral , Combinação de Medicamentos , Ácido Oxônico/uso terapêutico , Ácido Oxônico/administração & dosagem , Idoso , Estimativa de Kaplan-Meier
20.
World J Surg Oncol ; 22(1): 129, 2024 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-38734718

RESUMO

BACKGROUND: Colorectal cancer (CRC) presents with varying prognoses, and identifying factors for predicting metastasis and outcomes is crucial. Perineural invasion (PNI) is a debated prognostic factor for CRC, particularly in stage I-III patients, but its role in guiding adjuvant chemotherapy for node-positive colon cancer remains uncertain. METHODS: We conducted a single-center study using data from the Colorectal Section Tumor Registry Database at Chang Gung Memorial Hospital, Taiwan. This prospective study involved 3,327 CRC patients, 1,536 of whom were eligible after application of the exclusion criteria, to investigate the prognostic value of PNI in stage I-III patients and its predictive value for node-positive/negative cancer patients receiving adjuvant chemotherapy. Propensity score matching (PSM) was used to minimize selection bias, and follow-up was performed with standardized procedures. RESULTS: PNI-positive (PNI+) tumors were associated with higher preoperative CEA levels and more frequent adjuvant chemotherapy. After PSM, PNI + tumors were associated with marginally significantly lower 5-year disease-free survival (DFS) and significantly lower overall survival (OS) rates in stages III CRC. However, no significant differences were observed in stages I and II. Subgroup analysis showed that among PNI + tumors, only poorly differentiated tumors had higher odds of recurrence. PNI did not predict outcomes in node-negative colon cancer. Adjuvant chemotherapy benefited PNI + patients with node-positive but not those with node-negative disease. CONCLUSIONS: Our study indicates that PNI is an independent poor prognostic factor in stage III colon cancer but does not predict outcomes in node-negative disease. Given the potential adverse effects of adjuvant chemotherapy, our findings discourage its use in node-negative colon cancer when PNI is present.


Assuntos
Neoplasias do Colo , Invasividade Neoplásica , Estadiamento de Neoplasias , Nervos Periféricos , Pontuação de Propensão , Humanos , Feminino , Masculino , Neoplasias do Colo/patologia , Neoplasias do Colo/mortalidade , Neoplasias do Colo/tratamento farmacológico , Neoplasias do Colo/cirurgia , Pessoa de Meia-Idade , Prognóstico , Idoso , Estudos Prospectivos , Taxa de Sobrevida , Nervos Periféricos/patologia , Quimioterapia Adjuvante/métodos , Seguimentos , Metástase Linfática , Adulto , Taiwan/epidemiologia
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